title: Investigation of the protein alkylation sites of the STAT3:STAT3 inhibitor Stattic by mass spectrometry.
abstract: STAT3 (Signal Transducer and Activator of Transcription factor 3) is constitutively active in a wide range of human tumours. Stattic is one of the first non-peptidic small molecules reported to inhibit formation of the STAT3:STAT3 protein dimer complex. A mass spectrometry method has been developed to investigate the binding of Stattic to the un-phosphorylated STAT3βtc (U-STAT3) protein. Alkylation of four cysteine residues has been observed with possible reaction at a fifth which could account for the mechanism of action.
authors.affiliation: University College London School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Heidelberger
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zinzalla
authors.forename: Dyeison
authors.initials: D
authors.lastname: Antonow
authors.forename: Samantha
authors.initials: S
authors.lastname: Essex
authors.forename: B Piku
authors.initials: BP
authors.lastname: Basu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Palmer
authors.forename: Jarmila
authors.initials: J
authors.lastname: Husby
authors.forename: Paul J M
authors.initials: PJ
authors.lastname: Jackson
authors.forename: Khondaker M
authors.initials: KM
authors.lastname: Rahman
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Wilderspin
authors.forename: Mire
authors.initials: M
authors.lastname: Zloh
authors.forename: David E
authors.initials: DE
authors.lastname: Thurston
mesh_terms: D000477:Alkylating Agents / Q000737:chemistry; D000595:Amino Acid Sequence; D001665:Binding Sites; D003499:Cyclic S-Oxides / Q000737:chemistry*; D019281:Dimerization; D006801:Humans; D013058:Mass Spectrometry; D008958:Models, Molecular; D015394:Molecular Structure; D011506:Proteins / Q000737:chemistry; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors
chemical_list: D000477:Alkylating Agents; D003499:Cyclic S-Oxides; D011506:Proteins; D050796:STAT3 Transcription Factor; C517409:stattic
keywords: Cancer; Mass spectrometry; Protein:protein interaction inhibitor; STAT3